Reflecting the ever increasing complexity of modern society, a growing number of patients suffer from psychosomatic diseases that can effectively be treated with antianxiety drugs. Further, a fairly high percentage of these patients also suffer from depression which manifests itself various in the form of physical symptoms. In many of those cases, antianxiety drugs alone are incapable of alleviating such symptoms. Thus, in order to ensure that a patient's symptoms are alleviated while allowing them to live an ordinary social life, the development of a drug is desired that is free from the side effects of existing antianxiety agents, such as sleepiness and dizziness and which yet have an antidepressant action.
Benzodiazepine based drugs have heretofore been used widely as antianxiety drugs. However, side effects such as sleepiness and dizziness occur unavoidably in drugs of this group. Several drugs have been reported to exhibit an antidepressant action but their efficacy is weak.
Serotonin based antianxiety drugs have recently been developed as alternatives to the benzodiazepine based drugs. It has been reported that the serotonin based drugs are generally superior to the benzodiazepine based drugs in that the side effects they cause, such as sleepiness and dizziness, are alleviated (Eison, Psychopathology, 989; 22 (Suppl. 1): 13-20). Among the reported serotonin based drugs, Buspirone is already sold on the market as an antianxiety drug that causes lesser side effects but, at the same time, it is known to have an antidepressant action (Robinson et al., Psychopathology, 1989; 22 (Suppl. 1): 27-36). Further, Ipsapirone (Glaser, Drugs of the Future, 13 (5) 429 (1988) and Gepirone (Jenkins et al., J. Clin. Pharmacol., 1990; 10 (3, Suppl.): 775-855) have also been reported as serotonin-based drugs that have both antianxiety and antidepressant effects.
Japanese Patent Public Disclosure No. Hei 2-15059 teaches that compounds represented by the general formula (II): ##STR3## [where R.sub.a is 1-adamantyl, 3-methyl-1-adamantyl, 3-noradamantyl, unsubstituted or substituted 2-indolyl, 3-indolyl, 2-benzofuranyl or 3-benzofuranyl (a substituent, if any, is selected from among a lower alkyl, a lower alkoxy and a halogen): R.sub.b is an unsubstituted or substituted phenyl, benzyl, pyridinyl, pyrimidinyl or pyrazinyl (a substituent, if any, is selected from among a lower alkyl, a lower alkoxy, trifluoromethyl or a halogen); R.sub.c is hydrogen or a lower alkyl having 1-3 carbon atoms; p is an integer of 0 or 1; and q is an integer of 2-5] are useful as anxiety dispelling antidepressants.
All of these recently developed compounds are known to be antagonists for the serotonin 1A receptor. Drugs acting on this receptor are anticipated to work as antianxiety agents that are free from the side-effects of benzodiazepine based antianxiety agents and which yet lave an antidepressant action. Speaking of the serotonin receptor, it is known to play a role in counteracting the serotonin 2 receptor in the central nervous system (Gudelsky et al., Neuropharmacol., 1986, 25, 1307-1313; Davies et al., Soc. Neurosci. Abstr., 1987, 13, 801). Furthermore, two important facts have recently been reported: an antagonist against the serotonin 2 receptor exhibited an antianxiety action in an animal experiment (Stutzmann et al., Neurosclence Letters, 1991; 128, 4-8); and continuous administration of ipsaplrone caused a decrease in the intracerebral serotonin 2 receptor (Schechter et al., J. Pharmacol. Exptl. Ther. 1990; 225, 1335-1347). These facts suggest that in order to enhance the antianxiety and antidepressant actions of the antagonist for the serotonin 1A receptor, one may block the serotonin 2 receptor at the same time.